Podcast 42 - Estrogen: In a Nutshell

Estrogen in a Nutshell


Dr. Chad Edwards: This is Doctor Chad Edwards and you are listening to podcast number 42 of Against the Grain.

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Announcer: Welcome to Against the Grain Podcast with Doctor Chad Edwards, where he challenges the status quo when it comes to medicine. We get into hot topics in the medical field with real stories from real patients, to help you on your way to a healthy lifestyle. Get ready, because we’re about to go against the grain.

Marshall Morris: Hello, hello. This is the super tall Marshall Morris, and today I am joined by Doctor Chad Edwards, who believes that 80% of medical recommendations are crap, technically speaking here. He is the author of Revolutionize Your Health with Customized Supplements. He served in the U.S. army. He graduated from medical school at Oklahoma State University and he is the founder of revolutionhealth.org and Against the Grain podcast. Doctor Edwards welcome to the show here and you sir, you are a star. We’re around the country now. People are listening to the podcast and learning about all types of different topics including functional medicine. Welcome Tulsa prolotherapy.

Dr. Edwards: Why, thank you. Yes, I think we’ve got, what, 10 listeners now?

Marshall: We’ve got 10 listeners at least. I know that there are at least listening in every single week and so, what are we talking about today? What are we really getting into?

Dr. Edwards: This is such a big topic and I don’t mean colossal lots of loads of information. We’re going to distill it down into three-two-three-two. That’s how we’re going to break it down.

Marshall: Three-two-three-three-two.

Dr. Edwards: Yes. We’re going to take it off in bite size pieces and we’re going to work through this. But it is so common, in fact, I had a patient that came in today and she wanted, she was considering a hormone replacement. She felt awful. Her labs were — she was in menopause. She felt just absolutely terrible. I told her, “Hey, I think hormones would be a good way to go and I think pellets would be your ideal solution. It’s really convenient, easy and bioidentical and this will be great for you.” And she said, “Well, I hear you, but it’s not a breast cancer thing.” So, we had to stop and have this discussion about how that’s yet another piece of medical information is just pure crap Tulsa prolotherapy.

Marshall: Okay, so what we’re getting into estrogen as a hormone replacement and whether or not it’s related to breast cancer.

Dr. Edwards: Well, the breast cancer is only a piece of it. I’m going to explain why the answer is not that simple.

Marshall: Okay, cool. And if you’re wondering did he just say that maybe pellets are good solution? Go back and listen to the podcast where we talk about hormone pellets and it’s an awesome podcast where we get into the pros and cons of pellets.

Dr. Edwards: Yes, absolutely.

Marshall: Okay, so let’s get into it. What are we talking about here in terms of estrogen?

Dr. Edwards: Today, basically I just want to talk about estrogen. We’re going to break this down into like I said, three-two-three-two. So the first three, is there’s three different kinds of estrogen it’s a very important, in fact, it’s fundamental to understanding the literature that’s out there and the bad information that’s been disseminated about different things as far as different kinds of cancers. There’s three different kinds of estrogen. The second piece we’re going to cover is the two different kinds of estrogen receptors. We’re going talk about an alpha receptor and beta receptor. The next step is there’s three different pathways through which these hormones get metabolized and we’re going to break that down. Then the last step, is there is two — there is actually two different steps for this metabolism. So, three pathways, two steps in each pathway. We’re going to talk about each one of those and again and why these matter and why the answers for it’s estrogen. It’s not just estrogen. It’s much more complex than that.

Marshall: Okay. Let’s get into the three kinds of estrogen.

Dr. Edwards: The first thing is that there are three different kinds of estrogen in the human body. The first estrogen or well often abbreviated as E1 is estrone and that’s because there’s a single hydroxyl group on the estrogen backbone. I will get to the biochemistry of it but estrone that’s normally, naturally made of the human body. It is the dominant estrogen during women’s post-menopausal years. That is the primary estrogen after menopause. Second estrogen is estradiol, so named because it has two hydroxyl groups on the estrogen backbone. It’s often abbreviated as E2. And it is the dominant estrogen released from the ovaries, from the follicles specifically during menstruating years. So, that’s the estrogen that most women have you know through their young adult life, pubescent and young adult life. The third kind of estrogen is estriol or E3, so named because it has three hydroxyl groups on the estrogen backbone. That one is a very weak estrogen. Each of these three estrogens work and function differently. They’re dominant at different times in a woman’s life and they all play a little bit different role.
Rolling into the next component of this is the two different estrogen receptors. You have an alpha receptor and a beta receptor. The alpha receptor is pro-growth, the beta receptor is kind of anti-growth. These two different receptors when estrogens bind to these receptors doesn’t matter which estrogen it is. When they binds to these receptors, it triggers out the expression of target genes inside the cell which affect the growth, health and function of estrogen responsive tissues such as breast, uterus, ovaries, cervix prostate, testes, bone, etcetera. Vitamin B6 by the way helps to modulate the tissue responsiveness to those estrogens – so, just a little side note there Tulsa prolotherapy.
Now, the interesting thing so we’ve got three different estrogens – estrone, estradiol, estriol. Two different receptors – alpha and beta. This information is critical because each of these estrogens bind to the estrogen receptor at a little bit different affinity, actually vastly different affinities. Estrone is, like I said, the primary estrogen in postmenopausal years and it binds like 80% to the alpha estrogen receptor. Remember that alpha is a pro-growth estrogen receptor. So, 80% binding to alpha receptors. The estradiol is basically 50-50. It binds half to alpha, half to beta. You have pro-growth, anti-growth. It’s kind of a wash that net zero. [sneezes] Sorry about that. Then you have estriol which is [sic] primarily binds to the beta receptor, and it is a very weak estrogen.
When people will come to us and say, “Estrogen causes breast cancer.” Look at one of these hormones dominant estrone is in the in the post-menopausal years when is most breast cancer going to occur in the postmenopausal years, which estrogen binds to the pro-growth? When we talk about pro-growth, cancer is a pro-growth. So which one of these estrogens most likely plays a role? I don’t know a study that can definitively prove that but all of the physiology points in this direction. The offender is estrone because you are binding 80% to the pro-growth receptor, 20% to the anti-growth receptor.

Marshall: I’ve been taking notes and I agree.

Dr. Edwards: Thank you. The 80 and 20 should add up perfectly.
When you take estradiol, again, you get a 50-50 yet it’s a net wash. It’s not pro-growth, it’s not anti-growth. It’s just a net zero. The studies that have been done looking at like breast cancer and things like that and we’ve talked about this before. They were done on Premarin. Premarin, pregnant mares urine. The dominant estrogen in that, 50% of that, is estrone. So, you’re taking an oral estrogen which is known to increase risk of thromboembolic disease like blood clots. An oral estrogen that’s primarily estrone that’s binds to the alpha receptor 80% and is the pro-growth estrogen. Well, what do you expect? Of course you’re going to see more problems, more growth-related issues, more cancers associated with that estrogen. That just makes sense whereas estradiol which has not been in any of those studies does not have that same effect. So, we can’t say that estrogen causes a problem. There are no studies validating what I’m saying. But all of the studies that show that estrogen is a problem, primarily involve estrone. We can’t apply this data all the way across the board and say, “This goes back to that 80% medical recommendations of crap.” We take this little bit of information and we try to extrapolate it and it’s like if you tour Europe and they say, “Oh, you guys have guns. All of you guys are – you guys take guns into schools and shoot people.” There’s a few nut jobs that do that but most of us don’t do that. It’s the same thing you can’t make that prejudice call. Estrogen is not estrogen. It’s not estrogen. It’s different. Of course there’s some studies suggesting that estriol, that very weak estrogen that binds primarily to the beta receptor, is actually anti cancer. Not been proven definitively but there’s a lot of suggestion going that regard. Again when someone comes and they say, “I think estrogen causes breast cancer.” You go to look at what kind of estrogen is it. What receptor is it binding to. Three estrogens, two receptors each of them bind differently.

Marshall: Okay, we are going to take a quick break. We just covered the kinds of estrogen and the receptors and when we come back we’re going to get into the pathways and the different steps.

Dr. Edwards: Perfect.

Marshall: Boom.

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Marshall: Okay, and we are back joined here with Dr. Chad Edwards. We’re talking about estrogen. The three different kinds of estrogen and the two receptors of estrogen and now we’re going to get into the three different pathways for estrogen. Why don’t you begin walking us through that Dr. Edwards.

Dr. Edwards: Yes, those pathways are actually referring to estrogen metabolism.

Marshall: Metabolism.

Dr. Edwards: How we’re breaking them down. Total amount of estrogen in your body or total amount of anything in your body is based on how much you either intake or how much you produce, balanced with, how much you eliminate it or break it down. And the metabolism would be the breakdown of the elimination. The metabolism of estrogen is critical. There’s actually three different pathways that these estrogens can take. And there’s a — basically there’s a 2-hydroxy pathway, there’s a 4-hydroxy pathway and a 16-hydroxy pathway. The one that we want, the preferred ideal way to do this is going through the 2-hydroxy estradiol or estrone pathway. We add a hydroxy to it and it’s where we’re adding the hydroxy on the molecule, that’s for biochemical geeks like me, that dictates that molecule.
There are things that make estrogens or encourage estrogens to go through this pathway. One of them, as a supplement called Diindolylmethane. It’s actually a cruciferous vegetable like broccoli and those kinds of things. We find it there but you can take it as a supplement to help ensure the estrogens are metabolized the right way. When we do hormone pellets we strongly encourage patients to also take either Diindolylmethane or a combination of Diindolylmethane and Glucoraphanin which is the one that that we recommend to our client to help ensure the estrogens are being metabolized the right way. So, we have the two hydroxy pathway. The next best one is the 16-hydroxy estrone or estradiol pathway and there we’re adding that hydroxyl group into a different spot on the estrogen molecule and ultimately we make estriol through that pathway.
We still need some of that but it’s not as good as the two hydroxy pathway, the one that we want to avoid, kind of at all costs is the 4-hydroxy estrone pathway. Two is the best, 16 is the — it’s kind of like good, better, or the best. Or I should say, this one’s good, not good. The 4-hydroxy is the not good pathway.

Marshall: I hate it.

Dr. Edwards: And you should.

Marshall: Okay.

Dr. Edwards: I hope everyone picks up that “I hate it.”

Marshall: Tell me why I hate it.

Dr. Edwards: That’s beautiful. The reason that this is the worst one is because when we don’t methylate this thing and we’ll talk about that in just a second, when we don’t methylate it, then it converts into these 3, 4-quinones and 3, 4 quinones directly damage DNA and they are carcinogenic. This is where your cancers can be a much higher incidents, much higher risk. Interestingly, when you take in these equine estrogens from a Premarin, the pathway that it selects between the two, four and the 16 is the 4-hydroxy. That’s the path that it prefers Tulsa prolotherapy.

Marshall: So you have a pro-growth estrogen metabolizing in the 4-hydroxy pathway. It’s like a double whammy.

Dr. Edwards: Exactly. That’s exactly right. And then again if you don’t methylate well, if you want to know what methylation is, listen to our just –our previous podcast on MTHFR and methylation, and if you don’t methylate well, then you’re directly converting these things over to 3, 4-quinones and you got problems. And you’re much higher risk of cancer. The three different pathways, the 2-hydroxy which is the best, 16-hydroxy which is [sarcastically], 4-hydroxy which is I hate it as per Marshall.

Marshall: I’ve just now termed that. I hate it. Okay so so these are the phase one of this metabolism. What’s phase two? I know that we just touched on it but walk me through it.

Dr. Edwards: Yes, phase one is part of this detoxification pathway and that is hydroxylation. That’s phase one in these estrogen metabolisms. [coughs] Phase two is methylation and this produces good healthy estrogen metabolites and when we can methylate these things appropriately, then we don’t have buildup of toxic estrogen metabolites and we can eliminate them in a very expeditious and efficient manner. Again, go back and listen to our MTHFR methylation podcast and certainly listening to that in conjunction with this will help you understand why methylation is so important and how it can protect you from a number of things. One of them being estrogen metabolism and cancer and things like that. It’s that methylation step, making sure that you got good methylated B vitamins, trimethylglycine, knowing your MTHFR status. All of these kinds of things are important to make sure that you can enhance phase two detoxification which takes that two, four or 16-hydroxy estrogen into the two, four or 16 methoxy estrogen which we readily eliminate.
Very important to understand this process but I think it’s important for people to know hormones aren’t the problem. If estrogen – if estradiol caused cancer then our risk of cancer would be highest when estrogen is highest and that’s not what we see. Your estrogen levels are going to be highest in your pubescent years and early twenties.
That’s not when we see the predominance of breast cancers. It’s all these toxic metabolites. it’s these different kinds of estrogens. These crappy horse piss estrogens that we’re taking that selectively go through the 4-hydroxy and build up of 3, 4 quinones because we can’t methylate because we don’t know our MTHFR status and our vitamins and our nutritional status sucks. That’s what causes cancer. [coughs] It’s not estradiol and using bioidentical hormones Tulsa prolotherapy.

Marshall: Bringing this full circle to the patient that came into the clinic that maybe didn’t want to hear that maybe taking estrogen hormone pellets is the solution. How do you bring that full circle here?

Dr. Edwards: Basically just going back to understanding how these estrogens work in our body. How our nutritional status impacts this. What changes the three different levels. Which hormone is it that we’re using in the pellets. We’re using estradiol, bioidentical estradiol, that’s the hormone that you need, that’s the hormone that prevents the vasomotor symptoms, the hot flashes, those kinds of things. When you’ve got -when you add estradiol and you use appropriate nutritional supplementation with things like Glucoraphanin, Diindolylmethane and making sure that your nutritional status is good.

Marshall: Broccoli.

Dr. Edwards: Exactly. Especially if you are chopping broccoli. Yes, exactly.
When you do that, you’ve got good healthy estrogens in your body with good healthy estrogen metabolism in your body and there’s – I would argue there’s no need to worry about the concern with breast cancer.

Marshall: Cool. I’m going to just do a quick recap of everything that we covered today. I’ve been taking a furious notes here for the listeners.

Dr. Edwards: Let’s go for it. Let’s see how you do.

Marshall: Three different kinds of the estrogen. Estrogen is not just a one-trick pony. Okay, you see what I did there?

Dr. Edwards: I did.

Marshall: Okay, so, we got three kinds. We got estrone, estradiol and estrial.

Dr. Edwards: You got it.

Marshall: Okay, and then we have the two receptors. The pro-growth alpha receptors and the anti-growth beta receptors. And those three different estrogens will bind differently based on timing and the affinity for these different receptors. Then we have the three different pathways to metabolize the estrogen. We have the 2-hydroxy, the 4-hydroxy and the 16-hydroxy for the hydroxylation phase one part of process of the detoxification, and then the phase two is the methylation. Which if you want to learn more about that we can have you tune into the previous podcast here.

Dr. Edwards: You got it.

Marshall: I got it?

Dr. Edwards: You understand more about this. I’m being serious, you understand more about this than 99% of the physicians out there.

Marshall: Well, maybe I need to start my own clinic.

Dr. Edwards: You probably could.

Marshall: Dr. Edwards, thank you so much.

Dr. Edwards: Thanks Marshall.

Announcer: Thanks for listening to this week’s podcast with Dr. Chad Edwards. Tune in next week where we’ll be going against the grain.

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